Overexpression of Cancer-Associated Genes via Epigenetic Derepression Mechanisms in Gynecologic Cancer

Like other cancers, most gynecologic cancers are caused by aberrant expression of cancer-related genes. Epigenetics is one of the most important gene expression mechanisms, which contribute to cancer development and progression by regulating cancer-related genes. Since the discovery of differential gene expression patterns in cancer cells when compared with normal cells, extensive efforts have been made to explore the origins of abnormal gene expression in cancer. Epigenetics, the study of inheritable changes in gene expression that do not alter DNA sequence is a key area of this research. DNA methylation and histone modification are well-known epigenetic mechanisms, while microRNAs and alternative splicing have recently been identified as important regulators of epigenetic mechanisms. These mechanisms not only affect specific target gene expression but also regulate the functioning of other epigenetic mechanisms. Moreover, these diverse epigenetic regulations occur simultaneously. Epigenetic regulation of gene expression is extraordinarily complicated and all epigenetic mechanisms to be studied at once to determine the exact gene regulation mechanisms. Traditionally, the contribution of epigenetics to cancer is thought to be mediated through the inactivation of tumor suppressor genes expression. But recently, it is arising that some oncogenes or cancer-promoting genes (CPGs) are overexpressed in diverse type of cancers through epigenetic derepression mechanism, such as DNA and histone demethylation. Epigenetic derepression arises from diverse epigenetic changes, and all of these mechanisms actively interact with each other to increase oncogenes or CPGs expression in cancer cell. Oncogenes or CPGs overexpressed through epigenetic derepression can initiate cancer development, and accumulation of these abnormal epigenetic changes makes cancer more aggressive and treatment resistance. This review discusses epigenetic mechanisms involved in the overexpression of oncogenes or CPGs via epigenetic derepression in gynecologic cancers. Therefore, improved understanding of these epigenetic mechanisms will provide new targets for gynecologic cancer treatment

Metal/graphene sheets as p-type transparent conducting electrodes in GaN light emitting diodes

We demonstrate the use of graphene based transparent sheets as a p-type current spreading layer in GaN light emitting diodes (LEDs). Very thin Ni/Au was inserted between graphene and p-type GaN to reduce contact resistance, which reduced contact resistance from similar to 5.5 to similar to 0.6 Omega/ cm(2), with no critical optical loss. As a result, LEDs with metal-graphene provided current spreading and injection into the p-type GaN layer, enabling three times enhanced electroluminescent intensity compared with those with graphene alone. We confirmed very strong blue light emission in a large area of the metal-graphene layer by analyzing image brightness.open281

Phytosynthesis of Silver and Gold Nanoparticles Using the Hot Water Extract of Mixed Woodchip Powder and Their Antibacterial Efficacy

This study investigates the phytosynthesis, characterization, and antibacterial efficacy of silver and gold nanoparticles (NPs) produced using the hot water extract of mixed woodchip powder. The woodchip extract (WCE) was successfully used as both a reducing and stabilizing agent for the phytosynthesis of both crystalline metal NPs. The effects of different physicochemical factors affecting the formation of the metal NPs including reaction pH, concentration of the precursor metal salts, amount of WCE, and external energy input were evaluated. The characterization of the metal NPs was performed by transmission electron microscopy, selected area electron diffraction (SAED), energy dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD) pattern analysis. In addition, the antibacterial efficacy of the phytosynthesized NPs was measured. The AgNPs showed clear antibacterial activity against four representative bacterial strains. However, the AuNPs did not exhibit bactericidal activity, probably due to their surface modifications and relatively large size. These results suggest that the phytosynthesis of the metal NPs using WCE is highly efficient, and its convenience makes it suitable for use in large-scale production

Antigen-binding Characteristics of Circulating IgG Autoantibodies to Cytokeratin 18 Protein in Patients with Nonallergic Asthma

Cytokeratin 18 (CK18) protein was identified as an airway epithelial cell autoantigen associated with nonallergic asthma. Cleavage of CK18 protein by caspase-3 is a marker of early apoptosis in epithelial cells. It has been shown that the expression of active caspase-3 was increased in bronchial epithelial cells of asthmatic patients, when compared with healthy controls. To investigate the antigen-binding characteristics of IgG autoantibodies to CK18 protein in nonallergic asthma, the bindings of IgG autoantibodies to the fragments of CK18 protein cleaved by caspase-3 were analyzed by Western blot using serum samples from three patients with nonallergic asthma. Recombinant human CK18 protein was treated by caspase-3 and cleaved into N-terminal fragment (1-397 amino acids) and C-terminal fragment (398-430 amino acids). The binding capacity of IgG autoantibodies to N-terminal fragment of CK18 was maintained in one patient and reduced in other two patients. IgG autoantibodies from all three patients did not bind to C-terminal fragment of CK18. In conclusion, IgG autoantibodies to CK18 protein from patients with nonallergic asthma seems to preferentially bind to the whole molecule of CK18 protein and their antigen-binding characteristics were heterogeneous among the patients with nonallergic asthma

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition

Backgroundβ-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.MethodsApoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.ResultsAddition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.ConclusionGB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load

RNA-Guided Genome Editing in Drosophila with the Purified Cas9 Protein

We report a method for generating Drosophila germline mutants effectively via injection of the complex of the purified Cas9 protein, tracrRNA, and gene-specific crRNAs, which may reduce delayed mutations because of the transient activity of the Cas9 protein, combined with the simple mutation detection in GO founders by the T7E1 assay.

Hyeonggaeyeongyo-Tang for Treatment of Allergic and Nonallergic Rhinitis: A Prospective, Nonrandomized, Pre-Post Study

Hyeonggaeyeongyo-tang (HYT) is an ancient formula of oriental medicine traditionally used to treat rhinitis; however, clinical evidence has not yet been established. The aim of this study was to investigate the short-term and long-term efficacy and safety of HYT for chronic rhinitis. Adult subjects with chronic rhinitis symptoms were recruited. The subjects received HYT for 4 weeks and had follow-up period of 8 weeks. Any medicines used to treat nasal symptoms were not permitted during the study. The skin prick test was performed to distinguish the subjects with allergic rhinitis from those with nonallergic rhinitis. After treatment, the total nasal symptoms score and the Rhinoconjunctivitis Quality of Life Questionnaire score significantly improved in the whole subject group, in the allergic rhinitis group, and in the nonallergic rhinitis group, with no adverse events. This improvement lasted during a follow-up period of 8 weeks. Total IgE and eosinophil levels showed no significant difference after treatment in the allergic rhinitis group. HYT improved nasal symptoms and quality of life in patients with allergic rhinitis and nonallergic rhinitis. This is the first clinical study to evaluate the use of HYT to treat patients with rhinitis. This trial has been registered with the ClinicalTrials.gov Identifier NCT02477293

Immunoglobulin G Subclass Deficiency is the Major Phenotype of Primary Immunodeficiency in a Korean Adult Cohort

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases

Glycaemic status, insulin resistance, and risk of infection-related mortality:a cohort study

Importance: the impact of non-diabetic hyperglycaemia and insulin resistance on infection-related mortality risk remains unknown.Objective: we investigated the association of glycaemic status and insulin resistance with infection-related mortality in individuals with and without diabetes.Design: cohort study based on Kangbuk Samsung Health Study and national death records.Participants: about 666 888 Korean adults who underwent fasting blood measurements including glucose, glycated haemoglobin (HbA1c), and insulin during health-screening examinations were followed for up to 15.8 years.Main outcome and measures: infection-related mortality, therefore we used Cox proportional hazards regression analyses to estimate hazard ratios (HRs) and 95% CIs for infection-related mortality. Vital status and infection-related mortality were ascertained through national death records. Variable categories were created based on established cut-offs for glucose and HbA1c levels and homeostatic model assessment of insulin resistance (HOMA-IR) quintiles.Results: during a median follow-up of 8.3 years, 313 infectious disease deaths were dentified. The associations of glucose and HbA1c levels with infection-related mortality were J-shaped (P for quadratic trend&lt;.05). The multivariable-adjusted HR (95% CIs) for infection-related mortality comparing glucose levels &lt;5, 5.6-6.9, and ≥7.0 mmol/L to 5.0–5.5 mmol/L (the reference) were 2.31 (1.47–3.64), 1.65 (1.05–2.60), and 3.41 (1.66–7.00), respectively. Among individuals without diabetes, the multivariable-adjusted HR for infection-related mortality for insulin resistance (HOMA-IR ≥75th centile versus &lt;75th centile) was 1.55 (1.04–2.32).Conclusions and relevance: both low and high glycaemic levels and insulin resistance were independently associated with increased infection-related mortality risk, indicating a possible role of abnormal glucose metabolism in increased infection-related mortality.<br/

Growth direction determination of a single RuO2 nanowire by polarized Raman spectroscopy

The dependence of band intensities in the Raman spectrum of individual single-crystal ruthenium dioxide (RuO2) nanowires on the angle between the plane of polarization of the exciting (and collected) light and the long axis of the nanowire, is shown to be a simple, complementary technique to high resolution transmission electron microscopy (HRTEM) for determining nanowire growth direction. We show that excellent agreement exists between what is observed and what is predicted for the polarization angle dependence of the intensities of the nanowires' E-g (525 cm(-1)) and the B-2g (714 cm(-1)) Raman bands, only by assuming that the nanowires grow along the (001) crystallographic direction, as confirmed by HRTEM.open9